Process of preparing cyanine dyes from substituted mercapto derivatives



Patented June 4, 1940 UNITED STATES PATENT OFFICE PROCESS OF PREPARINGGYANINE DYES FROM SUBSTITUTED MERCAPTO DERIVA- TIVES Leslie G. S.Brookcr, Rochester, N. Y., assignor,

by mesneassignments, to Eastman Kodak Company, Rochester, N. Y., acorporation of New Jersey N0 Drawing. Application October 25, 1934,Serial No. 749,926

7 Claims.

tinuation-in-part of 'the copending application in the name of GraftonH. Keyes and myself Serial No. 739,127, filed August 9, 1934, whichdescribes the preparation of alkyl quaternary sub- -stitutedmercaptocyclammonium salts.

It'is well known that cyanine dyes of the tcyanine class, preferablyknown as the 2-cyanine class, may be prepared by condensing an alkylquaternary salt of a 2-iodopyridine or a 2-iodoquinoline with an alkylquaternary cyclammonium salt containing a reactive methyl group adjacentto the quinquivalent nitrogen atom. Many examples of such a reaction aregiven in my copending application Serial No. 651,870, filed January 16,1933. Now I have found that a similar condensation can be elfectedbetween an alkyl quaternary salt of a Z-(substituted-mercapto)- pyridineor a 2- (substituted-mercapta) -quinoline and an alkyl quaternarycyclammonium salt containing a reactive methyl group. I have furtherfound that the substituted-mercapto derivatives give rise to yieldscomparable with those obtained by using the iododerivatives and incertain cases give rise to even higher yields. Thus asubstituted-mercapto derivative will condense with an alkyl quaternarycyclammonium salt containing a reactive methyl group in the presence ofpyridine, whereas an iododerivative will not undergo a similarcondensation in the presence of pyridine. See my copending application,Serial No. 652,030, filed January 16, 1933. T

An object, therefore, of the present invention is to provide a processfor the preparation of 2'-cyanine dyes. 'A further object is to effectsuch a preparation by making use of alkyl quaternary salts ofz-(substituted-mercapto) -pyridines and/or 2 (substituted mercapto)quinolines. Other objects will appear hereinafter.

The alkyl quaternary salts of the substitutedmercapto-derivatives, usedherein, have the following structural formula:

wherein R represents an alkyl group such. as methyl, ethyl or n-butyl, Rrepresents an alkyl group such as methyl, ethyl or n-butyl or an arylgroup such as phenyl, p-tolyl, p-chlorophenyl, 2,5-dichlorophenyl,fl-naphthyl or a heterocyclic group such as benzothiazolyl orpyrazolonyl, A represents a vinylene, a phenylene or analkyl-substituted phenylene group and X represents anacid radical suchas halide, p-toluenesulfonate or any other suitable anion.

The alkyl quaternary cyclammonium salts containinga reactive methylgroup, which are used to condense with the substituted-mercaptoderivatives indicated above, have the following structural formula:

' lenium, A represents a phenylene, or a naphthylene group where 13represents oxygen, sulfur, selenium or a vinylene group and A representsa phenylene group where 13 represents a dimethylmethylene group.

A typical reaction of "my invention is illustrated by the followingequation:

C2115 I l-methylbenzothiazole ethiodlde o-om ounso Z-phonylthioqulnolineethiodide 1, 2-diethylthla-2'-cyanl ne iodide In addition to the alkylquaternary cyclammonium salts containing a reactive methyl group in theposition adjacent to the nitrogen atom, alkyl quaternary salts oflepidine or its derivatives can be used to condense with thesubstituted-mercapto derivatives. In such a condensation, a 2,4'-cyanine(isocyanine) dye is obtained. Such a reaction is illustrated by the2-phenylthioquinoline lepidine ethiodide ethiodide1,l-diethyl-2,4-cyonine iodide The condensations can be eifected in anybasic medium which does not adversely affect the reaction and whichfunctions to bind the elements of acid eliminated from the condensingmolecules. Triethylamine or pyridine is frequently employed. Whentriethylamine is used, a solvent for the reactants must be employed. Alower aliphatic alcohol, preferably absolute ethyl alcohol, is suitablefor such purpose. Pyridine acts as a solvent for the reacting molecules,in addition to absorbing the acid liberated from the condensingmolecules.

The condensation can be efiected with or without the application ofheat. However, heat is usually employed to accelerate the reaction.

Several examples of the preparation of 2'cyanine dyes will now bepresented. These dyes are representative of the many 2'cyanine dyeswhich could be prepared by the method herein recited.

EXAMPLE 1.-1',Z-diethyZthia-Z-cyanine iodide (a) 1.969 (1 mol.) of2-phenylthioquinoline ethiodide, 1.759 (1 mol.) of 1-methylbenzothiazoleetho-p-toluenesulfonate, 20 cc. of absolute ethyl alcohol and 1.0 g. (2mols.) of triethylamine were heated to boiling under reflux for severalminutes. The dye separated out in the hot. It was collected and washedwith water and with acetone. It was recrystallized from methyl alcohol.Melting point 283-4 C.

(b) When 0.5 g. (1 mol.) of triethylamine wasused, the yield of washeddye was slightly lower.

(c) Instead of heating the mixture, it was allowed to stand at roomtemperature for several days. After two days (using the amounts given ina) the yield was about 10% short of that obtained in (a), but rose tothe higher yield on standing a week.

Alternative methods follow:

0.37 g. (1 mol.) of 2-(n-butylthio)-quinoline ethiodide, 0.35 g. (1mol.) of l-methylbenzothiazole etho-p-toluenesulfonate, 10 cc. ofabsolute ethyl alcohol and 0.2 g. (2 mols.) of triethylamine were heatedto boiling under reflux for several minutes. After recrystallization thedye melted at 285-6 C. (Decomposition) 0.7 g. (1 mol.) ofl-methylbenzothiazole ethop-toluenesulfonate, 0.7 g. (1 mol.) ofZ-(n-propylthio) -quinoline ethiodide, 15 cc. of absolute ethyl alcoholand 0.4 g. (2 mols.) of triethylamine were heated to boiling underreflux for several minutes. After recrystallization from methyl alcohol,the dye melted at 281-5 C. (Decomposition) 0.5 g. (1 mol.)1-methylbenzothiazole etho-ptoluenesulfonate, 0.6 g. (1 mol.) ofZ-(p-chlorophenylthio) -quinoline ethiodide, 10 cc. of absolute ethylalcohol and 0.25 g. (2 mole.) of triethylamine were heated to boilingunder reflux for several minutes. After recrystallization from methylalcohol, the dye melted at 285-6" C. (Decomposition) 0.6 g. (1 mol.) of2-(2,5-diohlorophenylthio)- quinoline ethiodide, 0.5 g. (1 mol.)l-methylbenzothiazole etho-p-toluene sulfonate, 10 cc. of absolute ethylalcohol and 0.25 g. (2 mols.) of triethylamine were heated to boilingfor several minutes. After recrystallization from methyl alcohol, thedye melted at 285-6 C. (Decomposition.)

0.45 g. (1 mol.) of l-methylbenzothiazole ethop-toluenesulfonatc, 0.5 g.(1 mol.) of 2-(p-tolylthio) -quinoline ethiodide, 20 cc. of absoluteethyl alcohol and 0.25 g. (2 mols.) of triethylamine were heated toboiling under reflux for several minutes. After recrystallization frommethyl alcohol the dye melted at 285-6 C. (Decomposition.)

1.97 g. (1 mol.) of 2-phenylthioquinoline ethiodide. 1.76 g. (1 mol.) ofl-methylbenzothiazole etho-p-toluenesulfonate and about 12 cc. ofpyridine were boiled under reflux for several minutes. The precipitateddye was recrystallized from methyl alcohol and the recrystallized formmelted at about 283 C.

EXAMPLE 2.-1,Z-dicthylozra-Z-cyaninc iodide 1.45 g. (1 mol.) ofl-methylbenzoxazole ethiodide, 1.96 g. (1 mol.) of 2-phenylthioquinolineethiodide and 10 cc. of pyridine were boiled under reflux for severalminutes. After recrystallization from methyl alcohol, the dye melted at293-4 C. (Decomposition) EXAMPLE 3.-1-cthyZ-1,3,3-trimethylindo-2'-cyam'ne iodide 0.75 g. (1 mol.) of2,3,3-trimcthylindolenine methiodide, 0.98 g. (1 mol.) of2-phenylthioquinoline ethiodide and 5 cc. of pyridine were boiled underreflux for several minutes. After recrystallization from methyl alcohol,the dye melted at 204-5" C. (Decomposition) EXAMPLE4.-1,1'-diethyZ-2,2'-cyanine iodide 1.7 g. (1 mol.) of quinaldineethop-toluencsulfonate, 1.86 g. (1 mol.) of Z-phenylthioquinolineethiodide and 10 cc. of pyridine were boiled under reflux for severalminutes. After recrystallization [rom methyl alcohol, the dye melted at265-6 C. (Decomposition) EXAMPLE5.1',3-diethyl-4-phenylthiazolo-2'-cyamine iodide 0. 14 g. (1 mol.) of2-methyl-4-phenylthiazole and 0.5 g. (1 mol.) of ethylp-toluenesulfonate were heated in an oil bath at 110-120 C. for a fewhours. The crude salt thus formed, 1.0 g. (1 mol.) ofZ-phenylthioquinoline ethiodide, 20 cc. of absolute ethyl alcohol and0.5 g. (2 mols.) of triethylamine were heated to boiling under refluxfor several minutes. After recrystallization from methyl alcohol, thedye melted at 2535 C. (Decomposition.)

EXAMPLE 6.-1',3-diethylthiazolino-2'-oycmine T iodide g. (1 mol.) ofethyl p-toluenesulfonate were heated at 100 C. on the steam bath forsixhours. The salt thus formed, 1.0 g. (1 mol.) of 2-phenylthioquinolineethiodide, cc. .of absolute ethyl alcohol and 0.5 g. (2 mols.) oftriethylamine were heated to boiling under reflux for several minutes.After recrystallization from methyl alcohol the dye melted at 225-6 C.(Decomposition.)

EXAMPLE 7.1'-cthyl-2-methyl-3,4 benzothia-2' cyanine iodide 0.5 g. (1mol.) of 2-methyl-/3-naphthothiazole metho-p-toluenesulfonate, 0.5g. (1mol.) of 2- phenylthioquinoline ethiodide, 20 cc. of absolute ethylalcohol and 0.25 g. (2 mols.) of triethyl'- amine were heated to boilingunder reflux for several minutes. After recrystallization from methylalcohol, the dye melted at 267-8 C. (Decomposition.)

.After recrystallization from methyl alcohol, the

dye melted at 268-9 C.

EXAMPLE 9.1,1-dimethyZ-2-pyrido-2-cyanine iodide 1.2 g. (1 mol.) ofu-picoline methiodide, 1.9 g.

(1 mol.) of 2-phenylthioquinoline methiodide, 40 cc. of absolute ethylalcohol and 1.0 g. (2 mols.)

(Decomposition) of triethylamine were heated to boiling under I refluxfor several minutes. After recrystallization from methyl alcohol, thedye melted at 243-4 C. (Decomposition) EXAMPLE10.2-ethyl-1-methylthia-2-pyridocyanine iodide 0.95 g. (1 mol.) ofZ-(o-naphthylthio) -pyridine methiodide, 0.9 g. (1 mol.) ofl-methylbenzothiazole etho-p-toluene sulfonate 20 cc. of absolute ethylalcohol and 0.5 g. (2 mols.) of triethylamine were heated to boilingunder reflux for several minutes. After recrystallization from methylalcohol, the dye melted at 277-8 C. (Decomposition.)

EXAMPLE 11.1',3 -dimethyZthiaz0lino-2- pyridocyzmine iodide 0.25 g. (1mol.) of 2-methylthiazoline and 0.5 g. (1 mol.) ofmetho-p-toluenesulfonate were heated at 100 C. on a steam bath forseveral minutes. The salt thus formed; 1.0 g. (1 mol.) of 2-(5naphthylthio) pyridine methiodide, 10 cc. of absolute ethyl alcohol and0.5 g. (2 mol.) of triethylamine were heated to boiling under reflux forseveral minutes. After recrystallization from methyl alcohol, the dyemelted at 256-7 C. (Decomposition.)

EXAMPLE 12.3-ethyl 1', 4 dimethylthiaeolo- 2'-pyridocyanine iodide 0.7g. (1 mol.) of 2,4-dimethylthiazole ethiodicle, 0.95 g. (1 mol.) ofZ-(p-naphthylthio) -pyridine methiodide, 10 cc. of absolute ethylalcohol and 0.5 g. (2 mol.) of triethylamine were heated to boilingunder reflux for several minutes. After recrystallization from methylalcohoL-the dye melted at 265-6 C. v (Decomposition) EXAMPLE13.-1',2-diethyl-6'-methylthia-2'-cyanine iodide 0.23 g. (1 mol.) ofl-methylbenzothiazole ethop-toluene sulfonate, 0.3 g. (1 mol.) offi-methyl- 2-( 3-naphthylthio) -quinoline ethiodide, 10 cc. of absoluteethyl alcohol and 0.25 g. of triethylamine were heated to boiling underreflux for several minutes. After recrystallization from methyl alcohol,the dye melted at 281-3 C. (Decomposition.)

In the foregoing examples the yields are generally satisfactory, varyingfrom 30% to 95%.

The process described herein is a very general one. In its broadeststatement, any salt of a 2- alkyl (aryl or heterocyclic) thioderivativeof i a pyridine or quinoline base can be condensed with any alkylquaternary cyclammonium salt which contains a reactive methyl group. Theresult of such a condensation is a 2-cyanine salt when the reactivemethyl group is in the position alpha or adjacent to the quinquivalentnitrogen atom, and a 2,4'-cyanine salt when the reactive methyl group isin the position gamma to or opposite the quinquivalent nitrogen.

What I claim as my invention and desire to secure by Letters Patent ofthe United States isf 1. A process for preparing a cyanine dyecomprising condensing, in the presence of a basic condensing agent, acyclammonium alkyl quaternary salt containing a reactive methyl groupwith a cyclammonium alkyl quaternary salt of the following generalformula:

wherein A represents an organic group selected from the group consistingof vinylene and phenylene groups, R represents an alkyl group, Rrepresents an aryl group selected from the group consisting of arylgroups of the benzene series and aryl groups of the naphthylene seriesand X represents an acid radical.

2. A process for preparing a cyanine dye comprising condensing, in thepresence of a trialkylamine condensing agent, a cyclammonium alkylquaternary salt containing a reactive methyl group with a cyclammoniumalkyl quaternary salt of the following general formula:

r \CH A I CSR' n x wherein A represents an organic group selected fromthe group consisting of vinylene and phenylene groups, R represents analkyl group, R represents an aryl group selected from the groupconsisting of aryl groups of the benzene series and aryl groups of thenaphthylene series and X represents an acid radical.

3. A process for preparing a cyanine dye comprising condensing, in thepresence of a basic condensing agent, a cyclammonium alkyl quaternarysalt containing a reactive methyl group with a cyclainmonium alkylquaternary salt of the following general formula:

R X wherein A represents an organic group selected from the groupconsisting of vinylene and phenylene groups, R represents an alkyl groupand X represents an acid radical.

4. A process for preparing a cyanine dye comprising condensing, in thepresence of a trialkylamine condensing agent, a cyclammoniurn alkylquaternary salt containing a reactive methyl group with a cyclammoniumalkyl quaternary salt of the following general formula:

wherein A represents an organic group selected from the group consistingof vinylene and phenylene groups, R represents an alkyl group and Xrepresents an acid radical.

5. A process for preparing a cya-nine dye comprising condensing, in thepresence of a pyridine condensing agent, a cyclammonium alkyl quaternarysalt containing a reactive methyl group with a cyclammonium alkylquaternary salt of the following general formula:

wherein A represents an organic group selected from the group consistingof vinylene and phenylene groups, R represents an alkyl group and Xrepresents an acid radical.

6. A process for preparing a oyanine dye comprising condensing, in thepresence of pyridine condensing agent, one molecular proportion of 1-methylbenzothiazole etho p toluenesulfonate with one molecularproportion of 2-phenylthioquinoline ethiodide.

'7. A process for preparing a cyanine dye comprising condensing, in thepresence of triethylamine condensing agent, one molecular proportion ofl-methylbenzoxazole ethiodide with one molecular proportion of2-phenylthioquinoline ethiodide.

LESLIE G. S. BROOKER.

